Uveal melanoma is a malignancy of the eye that occurs in approximately five to eight people per million per year. Common symptoms include blurred vision, eye pain, redness, floaters, and irritation. Uveal melanoma is the most common primary intraocular malignancy, and while several local therapies can be offered for primary disease control such as plaque brachytherapy, proton therapy and enucleation, effective therapies to control distant disease have been limited.
Two to three percent of cases present with metastasis at the time of diagnosis. Most common sites are liver (90%), lungs, bones, soft tissue. Risk of metastasis is estimated at up to 50% of those diagnosed. Regardless of cell type or stage, recurrence or relapse carries a poor prognosis. Distant recurrence of uveal melanoma has traditionally been associated with mortality within twelve to eighteen months. Cause of death is generally due to metastatic disease. Overall five-year survival is approximately 80%.
Use of genetic testing at the time of primary diagnosis is now recommended in order to identify patients who are at high risk for metastatic disease. Enhanced screening and imaging of the liver and lungs allow for identification of early disease. Improvements in liver-directed therapy along with systemic chemotherapy and immunotherapy have improved life expectancy of those with this disease.
The HEPZATO KIT delivery system, an advanced liver-directed therapy, was approved by the FDA in August 2023. It is the first and only liver-directed, high-dose chemotherapy for metastatic uveal melanoma in adult patients with unresectable hepatic metastases. The HEPZATO KIT is a combination of high dose melphalan (chemotherapy) plus a specialized delivery system. [Melphalan meets National Comprehensive Cancer Network (NCCN) guidelines as a recommended liver-directed therapy.] This treatment first became available in US hospitals in January 2024.
Administration of HEPZATO requires general anesthesia and extracorporeal bypass of circulation; the procedure isolates the liver blood supply while limiting systemic exposure. Melphalan is administered by infusion into the patient’s hepatic artery for thirty minutes, followed by a thirty-minute washout. This treatment can be given every six to eight weeks for up to six total infusions.
The HEPZATO KIT is only available through the HEPZATO KIT Risk Evaluation and Mitigation Strategy (REMS) program and the facility must follow the REMS protocol to obtain the kit. Before administration, the facility must obtain an authorization to dispense by contacting the REMS Coordinating Center to verify the procedure team is qualified to perform the procedure and administer the drug. In the US, only fifteen hospitals are currently approved to administer HEPZATO, with a goal of thirty-five hospitals by the end of the year.
The average wholesale price of the HEPZATO KIT is $219,000 per cycle, with a maximum of six cycles as noted above. This does not include the cost of hospital admission, administration, and operating room services which will include extracorporeal bypass of circulation. In clinical trials, the average number of infusions was four, with 37% of the 91 patients treated receiving the maximum six infusions.
Summary
The HEPZATO KIT is FDA approved to treat uveal melanoma in adults with unresectable liver metastasis.
This is another tool to manage metastatic disease. It is best used in experienced centers with melanoma expertise.
The kit is part of the REMS program with limited suppliers, and facilities require certification to perform the procedure and administer the drug.
The procedure may be repeated for a total of six infusions, six to eight weeks apart. Clinical trial data shows the average number of infusions was four.
Average wholesale price is $219,000. Multiply this by four and the cost is $876,000 for the average number of cycles of treatment, excluding hospitalization and other charges. Depending on cost of kit, length of stay and number of cycles/procedures, total cost could well be in excess of $1 million.
Given the low number of facilities that are currently qualified to perform this procedure, there is a high probability this treatment may be out of network.
An independent physician review may be helpful along with negotiations for cost prior to hospitalization.
Please contact your Summit Re representative as soon as you become aware of a request for HEPZATO. Our Summit ReSources managed care staff is available to answer any questions or concerns you may have. We will continue to investigate and provide information to our clients as this field of medicine continues to evolve.
Article written by Ginny Fisher, RN, BSN, CCM, Managed Care Specialist for Summit Reinsurance Services, Inc. For more information about how this may affect your plan, please contact your Summit ReSources care specialist. The following sources provided information for this article:
ETS
Interlink
AMS
MedScape